Mucoadhesive-to-penetrating controllable peptosomes-in-microspheres co-loaded with anti-miR-31 oligonucleotide and Curcumin for targeted colorectal cancer therapy

Ran Zhao, D. U. Sujuan, Ying Liu, L. V. Cong, Yongli Song, Xinchun Chen, Bing Zhang, Dan Li, Shan Gao, C. U.I. Wei, Maksim V. Plikus, Xiaohua Hou, Kaichun Wu, Zhanju Liu, Zhihua Liu, Yingzi Cong, Yuan Li, Zhengquan Yu

Research output: Contribution to journalArticle

Abstract

Background: Accumulating evidences indicate that nanomedicines greatly decrease the side effects and enhance the efficacy of colorectal cancer (CRC) treatment. In particular, the use of rectal delivery of nanomedicines, with advantages such as fast therapeutic effects and a diminishing hepatic first-pass effect, is currently emerging. Method: We established a CRC targeted delivery system, in which α-lactalbumin peptosomes (PSs) co-loaded with a microRNA (miR)-31 inhibitor (miR-31i) and curcumin (Cur) were encapsuslated in thiolated TEMPO oxidized Konjac glucomannan (sOKGM) microspheres, referred as sOKGM-PS-miR-31i/ Cur. The CRC targeting capability, drug release profiles, mucoadhesive-to-penetrating properties and therapeutic efficacy of sOKGM-PS-miR-31i/Cur delivery system were evaluated in colorectal cancer cells and azoxymethane-dextran sodium (AOM-DSS) induced tumor models. Results: sOKGM-PS-miR-31i/Cur delivery system were stable in the harsh gastrointestinal environment after rectal or oral administration; and were also mucoadhesive due to disulfide bond interactions with the colonic mucus layer, resulting in an enhanced drug retention and local bioavailability in the colon. Concomitantly, the released PS-miR-31i/Cur PSs from the microsphere was mucus-penetrating, efficiently passing through the colonic mucus layer, and allowed Cur and miR-31i specifically target to colon tumor cells with the guide of CD133 targeting peptides. Consequently, rectal delivery of sOKGM-PS-miR-31i/Cur microspheres suppressed tumor growth in an azoxymethane-dextran sodium sulfate (AOM-DSS)-induced tumor model. Conclusion: sOKGM-PS-miR-31i/Cur microspheres are effective rectal delivery system with combined advantages of mucoadhesive and mucus-penetrating properties, representing a potent and viable therapeutic approach for CRC.

Original languageEnglish (US)
Pages (from-to)3594-3611
Number of pages18
JournalTheranostics
Volume10
Issue number8
DOIs
StatePublished - 2020

Keywords

  • Anti-colorectal cancer therapy
  • Anti-microRNA oligonucleotide
  • Mucoadhesive-to-penetrating
  • Oral delivery
  • Peptosomes-in-microsphere
  • Rectal delivery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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  • Cite this

    Zhao, R., Sujuan, D. U., Liu, Y., Cong, L. V., Song, Y., Chen, X., Zhang, B., Li, D., Gao, S., Wei, C. U. I., Plikus, M. V., Hou, X., Wu, K., Liu, Z., Liu, Z., Cong, Y., Li, Y., & Yu, Z. (2020). Mucoadhesive-to-penetrating controllable peptosomes-in-microspheres co-loaded with anti-miR-31 oligonucleotide and Curcumin for targeted colorectal cancer therapy. Theranostics, 10(8), 3594-3611. https://doi.org/10.7150/thno.40318